Gene Expression Grouping Can Predict Treatment Response in Ulcerative Colitis, Study Suggests

Gene Expression Grouping Can Predict Treatment Response in Ulcerative Colitis, Study Suggests

People with ulcerative colitis can be divided into groups based on gene expression, and this division can help identify those more likely to respond to treatments, a recent study found.

Titled, “Conserved transcriptomic profile between mouse and human colitis allows unsupervised patient stratification,” the study was published in Nature Communications.

Biological medicines, such as Ixifi (infliximab) and Entyvio (vedolizumab), are mainstays of treatment for inflammatory bowel disease (IBD), which encompasses both ulcerative colitis and Crohn’s disease. However, only around half of IBD patients will have a response to these therapeutics. This variability in treatment response — as well as variations in how the disease itself presents, person to person — is a major obstacle for getting affected people effective treatment.

Identifying the individuals most likely to respond — or to not respond — to treatments is, therefore, a goal of research in this field.

To learn more, researchers at the Karolinska Institutet in Sweden attempted to classify ulcerative colitis based on gene expression — that is, which genes are “turned on” or “turned off,” and to what extent.

They first collected colon biopsies from 102 ulcerative colitis patients, and measured gene expression. But there was too much variability among the patients to classify them into a few overarching groups.

Then, the researchers had an idea: what if they focused only on the genes that are critical to the progression of the disease, rather than looking at gene expression globally?

To do this, the investigators turned to a mouse model of ulcerative colitis. By comparing data from both species, they identified 57 genes that were dysregulated — that is, expressed at abnormally high or low levels — in both mice and humans.

Using this panel of genes, the researchers divided the human patients into two groups, which they named UC1 (60 patients) and UC2 (42 patients). Specifically, those in the UC1 group were characterized by a gene expression profile that favored the recruitment and activity of neutrophils, a type of immune cell.

The researchers then looked at how participants in both groups responded to treatment with biological medicines. UC1 patients were, overall, less likely to respond to these therapies. Response rates in this group were 13% for Entyvio, and less than 10% for Ixifi. In contrast, 60% of UC2 patients responded to Entyvio, and 70% responded to Ixifi.

“We demonstrate the principle that it’s possible to combine datasets from mice and humans to group previously indistinguishable patients. The results provide new knowledge on inflammatory bowel diseases and can contribute to the more tailored treatment of ulcerative colitis,” Eduardo Villablanca, PhD, a professor at Karolinska Institutet and co-author of the study, said in a press release.

The scientists said the groupings are obviously still imperfect as predictors of treatment response, and note the study is relatively small, meaning more research is needed.

Still, this study does act as a proof-of-concept, and Villablanca believes this method also might yield useful results if applied to other diseases.